Orally and transdermally replaced estradiol improves endothelial function equally in middle-aged women after surgical menopause

Objective: Improvement in endothelial function may be an important mechanism by which estrogen replacement therapy protects postmenopausal women against coronary artery disease. We determined whether the vascular effects of estradiol depend on the route of administration. Study Design: Six weeks after surgically induced menopause, 43 healthy women were assigned randomly to 28 weeks of treatment by either orally or transdermally replaced estradiol. Endothelium-dependent and endothelium-independent dilation were calculated with the use of the diameters of the brachial artery that were measured at rest by high resolution ultrasound scanning after reactive hyperemia and after sublingual glyceryl trinitrate. Results: Endothelium-dependent dilation increased after oral estradiol replacement from 6% ± 3.9% to 13.2% ± 4.4% (P< .0001) and after transdermal estradiol replacement from 7% ± 4.9% to 14.9% ± 5.6%(P< .0001). Endothelium-independent dilation did not change significantly in either group. The improvements in endothelium-dependent dilation after estrogen substitution were independent of the changes in blood lipids and lipoproteins. Conclusion: Both oral and transdermal long-term replacement of estradiol lead to improved endothelial function in healthy middle-aged women after surgically induced menopause.